Role of PGC-1α in tumorigenesis in vitro and in vivo

Resumen del póster presentado al 2nd Symposium on Biomedical Research: "Advances and perspectives in cancer", celebrado en Madrid el 17 de abril de 2015.-- et al.Warburg effect is a major characteristic of cancer cells, a metabolic change that drives higher levels of glycolysis and lactate production in contrast to oxidative phosphorilation of normal cells, even in aerobic conditions, a typical pathway in normal cells during anaerobic conditions. PGC-1α is a master regulator of mitochondrial metabolism and it role in mitochondrial biogenesis and upregulation of electron chain transport components is well-known. The aim of the study was to determine the possible role of PGC-1α in tumorigenesis. To test this idea, we used WT and PGC-1α KO MEFs that were serially passed till they reach cellular senescence and immortalized spontaneously. Our results show that in the absence of PGC-1α MEFs produce higher levels of mitochondrial reactive oxygen species and accumulate more oxidative DNA damage, leading to an early induction of senescence markers. However, cell proliferation rate was not significantly different between WT and KO MEFs regardless of passage number. Importantly, PGC-1α KO MEFs showed and early escape from senescence, compared to WT MEFs. Three lines of immortalized WT and three of immortalized KO MEFs were further analyzed for their oncogenic potential. In vitro studies showed that KO MEFs showed a more accelerated non-oriented migration, reduced contact-inhibition and increased capacity to form colonies in soft agar. In vitro, proliferation rates where not significantly different between WT and KO immortalized MEFs. In vivo, tumor formation capacity was directly tested by subcutaneous injection of the immortalized cell lines. We found that in vivo, PGC-1α KO MEFs formed larger and more proliferative tumors. These results support a potential role of PGC-1α as a tumor suppressor gene.Peer reviewe